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| {{Infobox_Disease | | | __NOTOC__ |
| Name = {{PAGENAME}} |
| | {{Transmissible spongiform encephalopathy}} |
| Image = |
| | {{CMG}}; {{AE}} {{KS}} {{RAB}} |
| Caption = |
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| DiseasesDB = 25165 |
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| ICD10 = A81 |
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| ICD9 = {{ICD9|046}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = neuro |
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| eMedicineTopic = 662 |
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| MeshID = |
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| }} | |
| {{EH}} | |
| '''Transmissible spongiform encephalopathies''' ('''TSEs''', also known as '''prion diseases''') are a group of progressive conditions that affect the [[brain]] and [[nervous system]] of [[human]]s and [[animal]]s and are transmitted by [[prion]]s. Mental and physical abilities deteriorate and myriad tiny holes appear in the [[Cerebral cortex|cortex]] causing it to appear like a sponge (hence 'spongiform') when brain tissue obtained at [[autopsy]] is examined under a [[microscope]]. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time. Prion diseases of humans include classic [[Creutzfeldt-Jakob disease]], new variant Creutzfeldt-Jakob disease (a human disorder related to [[mad cow disease]]), [[Gerstmann-Sträussler-Scheinker syndrome]], [[fatal familial insomnia]] and [[kuru (disease)|kuru]]. These conditions form a spectrum of diseases with overlapping signs and symptoms.
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| Unlike other kinds of infectious disease which are spread by [[microbe]]s, the infectious agent in TSEs is a specific [[protein]] called [[prion]] protein. Misshaped prion proteins carry the disease between individuals and cause deterioration of the [[brain]]. TSEs are unique diseases in that their [[aetiology]] may be genetic, sporadic or infectious via ingestion of infected foodstuffs and via [[Iatrogenesis|iatrogenic]] means (e.g. blood transfusion) (reviewed in Prusiner, 1991; Collinge, 2001). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare [[mutation|mutant]] prion [[allele]], which expresses prion proteins that contort by themselves into the disease-causing [[protein structure|conformation]]. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In recent times a type of TSE called [[bovine spongiform encephalopathy]] (BSE) spread in [[cattle]] in an epidemic fashion. This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. The epidemic could have begun with just one cow with sporadic disease.
| | '''For patient information, click [[Transmissible spongiform encephalopathy (patient information)|here]]''' |
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| | {{SK}} TSE; prion diseases |
| | == [[Transmissible spongiform encephalopathy overview|Overview]] == |
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| Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal [[sterilization]] procedures such as boiling or irradiating materials fail to render prions non-infective.
| | == [[Transmissible spongiform encephalopathy historical perspective|Historical Perspective]] == |
| | == [[Transmissible spongiform encephalopathy pathophysiology|Pathophysiology]] == |
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| ==Classification== | | == [[Transmissible spongiform encephalopathy causes|Causes]] == |
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| <table border="1" style="border-collapse:collapse;" width="98%">
| | == [[Transmissible spongiform encephalopathy differential diagnosis|Differentiating Transmissible spongiform encephalopathy from other Diseases]] == |
| <tr bgcolor="lightblue">
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| <th colspan="5">[[Mammal]]ian agents of spongiform encephalopathies</th>
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| </tr>
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| <tr>
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| <th>[http://www.ncbi.nlm.nih.gov/ICTVdb/ ICTVdb] Code</th>
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| <th>Disease name</th>
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| <th>Natural host</th>
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| <th>Prion name</th>
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| <th>PrP [[isoform]]</th>
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| </tr>
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| <tr>
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| <td>[http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/90.001.0.01.001.htm 90.001.0.01.001.] </td>
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| <td>[[Scrapie]]</td>
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| <td>[[Sheep]] and [[goat]]s</td>
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| <td>Scrapie prion</td>
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| <td>OvPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.002. </td>
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| <td>[[Transmissible mink encephalopathy]] (TME)</td>
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| <td>[[Mink]]</td>
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| <td>TME prion</td>
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| <td>MkPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.003. </td>
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| <td>[[Chronic wasting disease]] (CWD)</td>
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| <td>[[Elk]], [[White-tailed deer]], [[Mule Deer]] and [[Red Deer]]</td>
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| <td>CWD prion</td>
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| <td>MDePrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.004. </td>
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| <td>[[Bovine spongiform encephalopathy]] (BSE)</td>
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| <td>[[Cattle]]</td>
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| <td>BSE prion</td>
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| <td>BovPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.005. </td>
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| <td>[[Feline spongiform encephalopathy]] (FSE)</td>
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| <td>[[Cats]]</td>
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| <td>FSE prion</td>
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| <td>FePrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.006. </td>
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| <td>[[Exotic ungulate encephalopathy]] (EUE)</td>
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| <td>[[Nyala]] and [[Greater Kudu|greater kudu]]</td>
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| <td>EUE prion</td>
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| <td>NyaPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.007. </td>
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| <td>[[Kuru (disease)|Kuru]]</td>
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| <td>[[Humans]]</td>
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| <td>Kuru prion</td>
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| <td>HuPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.008. </td>
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| <td>[[Creutzfeldt-Jakob disease]] (CJD)</td>
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| <td>Humans</td>
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| <td>CJD prion</td>
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| <td>HuPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td> </td>
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| <td>(New) Variant Creutzfeldt-Jakob disease (vCJD, nvCJD)</td>
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| <td>Humans</td>
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| <td>vCJD prion</td>
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| <td>HuPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.009. </td>
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| <td>[[Gerstmann-Sträussler-Scheinker syndrome]] (GSS)</td>
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| <td>Humans</td>
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| <td>GSS prion</td>
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| <td>HuPrP<sup>Sc</sup></td>
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| </tr>
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| <tr>
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| <td>90.001.0.01.010. </td>
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| <td>[[Fatal familial insomnia]] (FFI)</td>
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| <td>Humans</td>
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| <td>FFI prion</td>
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| <td>HuPrP<sup>Sc</sup></td>
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| </tr>
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| </table>
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| ==Features of TSE== | | == [[Transmissible spongiform encephalopathy epidemiology and demographics|Epidemiology and Demographics]] == |
| The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, [[neuron]]al loss, [[astrocyte|astrocytosis]] and [[amyloid]] plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a [[primate]] in 1966, followed by CJD in 1968 and GSS in 1981.These neuropathological features have formed the basis of the [[histology|histological]] diagnosis of human prion diseases for many years, although it was recognised that these changes are enormously variable both from case to case and within the [[central nervous system]] in individual cases.<ref>{{cite journal | author=Jeffrey M, Goodbrand IA, Goodsir CM | title=Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure | journal=Micron | year=1995 | pages=277-98 | volume=26 | issue=3 | id=PMID 7788281}}</ref>
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| The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as [[Clinical depression|depression]], lack of coordination, and/or an unsteady gait ([[ataxia]]). Patients also may experience involuntary jerking movements called [[myoclonus]], unusual sensations, [[insomnia]], confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment ([[dementia]]) and lose the ability to move or speak.<ref>{{cite journal | author=Collinge J | title=Prion diseases of humans and animals: their causes and molecular basis | journal=Annu Rev Neurosci | year=2001 | pages=519-50 | volume=24 | id=PMID 11283320}}</ref>
| | == [[Transmissible spongiform encephalopathy risk factors|Risk Factors]] == |
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| Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.
| | == [[Transmissible spongiform encephalopathy natural history, complications and prognosis|Natural History, Complications and Prognosis]] == |
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| Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt-Jakob disease has been transmitted to patients taking injections of [[growth hormone]] harvested from human [[pituitary gland]]s, and from instruments used for [[brain surgery]] (Brown, 2000) (prions can survive the "[[autoclave]]" sterilization process used for most surgical instruments). It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when [[cannibalism]] or similar practices allow the proteins to accumulate over more than one generation. An example is [[kuru (disease)|kuru]], which reached epidemic proportions in the mid 20th century in the [[Fore (people)|Fore]] people of [[Papua New Guinea]], who used to consume their dead as a funerary ritual.<ref>{{cite journal | author=Collins S, McLean CA, Masters CL | title=Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies | journal=J Clin Neurosci | year=2001 | pages=387-97 | volume=8 | issue=5 | id=PMID 11535002}}</ref> Laws in developed countries now proscribe the use of [[rendering (industrial)|rendered]] [[ruminant]] proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.
| | ==[[Major or mild neurocognitive disorder due to prion disease| Major or Mild Neurocognitive Disorder Due to Prion Disease]]== |
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| Note that not all [[encephalopathy|encephalopathies]] are caused by prions, as in the cases of [[Progressive multifocal leukoencephalopathy|PML]] (caused by the [[JC virus]]), [[CADASIL]] (caused by abnormal NOTCH3 protein activity), and [[Krabbe disease]] (caused by a deficiency of the [[enzyme]] galactosylceramidase). [[Progressive spongiform leukoencephalopathy|PSL]] -- which is a spongiform encephalopathy -- is also probably not caused by a prion, although the adulterant which causes it among [[heroin]] smokers has not yet been identified ([http://www.hafci.org/infoline/enu/heroin.htm], [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10563626&dopt=Abstract], [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9308333&dopt=Abstract], [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11965173&dopt=Abstract]). This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms.
| | == Diagnosis == |
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| ==Genetics==
| | [[Transmissible spongiform encephalopathy history and symptoms|History and Symptoms]] | [[Transmissible spongiform encephalopathy physical examination|Physical Examination]] | [[Transmissible spongiform encephalopathy laboratory findings|Laboratory Findings]] | [[Transmissible spongiform encephalopathy other diagnostic studies|Other Diagnostic Studies]] |
| Mutations in the [[PRNP]] [[gene]] cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.
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| The PRNP gene provides the instructions to make a protein called the [[prion protein]] (PrP). Normally, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-[[Mutation]]s in this gene cause cells to produce an abnormal form of the prion protein, known as PrP<sup>Sc</sup>. This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease.
| | == Treatment == |
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| Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.
| | [[Transmissible spongiform encephalopathy medical therapy|Medical Therapy]] | [[Transmissible spongiform encephalopathy primary prevention|Primary Prevention]] | [[Transmissible spongiform encephalopathy cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Transmissible spongiform encephalopathy future or investigational therapies|Future or Investigational Therapies]] |
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| In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.
| | ==Case Studies== |
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| ==Epidemiology==
| | [[Transmissible spongiform encephalopathy case study one|Case #1]] |
| These spontaneous disorders in humans are very rare affecting only about one person per million worldwide each year. However, transmissible TSEs can reach epidemic proportions as was seen in the UK BSE outbreak of the 80s and 90s. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that if animals start to show the disease after an outbreak on a nearby farm then you cannot show that it is the same strain affecting both, suggesting transmission, or that the second outbreak came from a completely different source.
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| ===A List of Prion Diseases===
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| Listed below are the prion diseases identified to date. Click the linked diseases to go to their respective topic sites. CDC does not currently offer information here on every prion disease listed.
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| ====Human Prion Diseases====
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| * Creutzfeldt-Jakob Disease (CJD)
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| * Variant Creutzfeldt-Jakob Disease (vCJD)
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| * Gerstmann-Straussler-Scheinker Syndrome
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| * Fatal Familial Insomnia
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| * Kuru
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| ====Animal Prion Diseases====
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| * Bovine Spongiform Encephalopathy (BSE)
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| * Chronic Wasting Disease (CWD)
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| * Scrapie
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| * Transmissible mink encephalopathy
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| * Feline spongiform encephalopathy
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| * Ungulate spongiform encephalopathy
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| ==Possible cure or vaccine==
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| Recent research from the [[University of Toronto]] and [[Caprion Pharmaceuticals]] have discovered one possible avenue which might lead to quicker diagnosis, a vaccine or possibly even treatment for prion diseases. The abnormally folded proteins which cause the disease have been found to expose a [[side chain]] of amino acids which the properly folded protein does not expose. [[Antibodies]] specifically coded to this side chain amino acid sequence have been found to stimulate an immune response to the abnormal prions and leave the normal proteins intact. [http://www.sciencedaily.com/releases/2003/06/030602025719.htm]
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| Another idea involves using custom [[peptide]] sequences. Since some research suggests prions aggregate by forming beta barrel structures, work done ''in vitro'' has shown that peptides made up of beta barrel-incompatible [[amino acid]]s can help break up accumulations of prion. <!-- find link to article -->
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| Yet a third idea concerns [[gene therapy|genetic therapy]], whereby the [[gene|gene]] for encoding protease-resistant protein is considered to be an error in several species, and therefore something to be inhibited.
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| ==Notes==
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| ==References== | | ==References== |
| *''This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke, [[National Institutes of Health]] [http://www.ninds.nih.gov/health_and_medical/disorders/tse.htm] and the [[U.S. National Library of Medicine]] [http://ghr.nlm.nih.gov/condition=priondisease]'' | | *''This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke, [[National Institutes of Health]] [http://www.ninds.nih.gov/health_and_medical/disorders/tse.htm] and the [[U.S. National Library of Medicine]] [http://ghr.nlm.nih.gov/condition=priondisease]'' |
| * {{cite journal | author=Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, d'Aignaux JH, Cervenakova L, Fradkin J, Schonberger LB, Collins SJ | title=Iatrogenic Creutzfeldt-Jakob disease at the millennium | journal=Neurology | year=2000 | pages=1075-81 | volume=55 | issue=8 | id=PMID 11071481}} | | * {{cite journal | author=Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, d'Aignaux JH, Cervenakova L, Fradkin J, Schonberger LB, Collins SJ | title=Iatrogenic Creutzfeldt-Jakob disease at the millennium | journal=Neurology | year=2000 | pages=1075-81 | volume=55 | issue=8 | id=PMID 11071481}} |
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| * {{cite journal | author=Weissmann C | title=The state of the prion | journal=Nat Rev Microbiol | year=2004 | pages=861-71 | volume=2 | issue=11 | id=PMID 15494743}} | | * {{cite journal | author=Weissmann C | title=The state of the prion | journal=Nat Rev Microbiol | year=2004 | pages=861-71 | volume=2 | issue=11 | id=PMID 15494743}} |
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| ==External links== | | ==External Links== |
| *[http://www.ninds.nih.gov/health_and_medical/disorders/tse.htm ''Transmissible Spongiform Encephalopathy''] | | *[http://www.ninds.nih.gov/health_and_medical/disorders/tse.htm ''Transmissible Spongiform Encephalopathy''] |
| *[http://www.ninds.nih.gov/disorders/alzheimersdisease/alzheimersdisease.htm Neurodegenerative Disease.] | | *[http://www.ninds.nih.gov/disorders/alzheimersdisease/alzheimersdisease.htm Neurodegenerative Disease.] |
| *[http://www.ninds.nih.gov/disorders/alpersdisease/alpersdisease.htm Neurodegenerative disease: Encephalopathy.] | | *[http://www.ninds.nih.gov/disorders/alpersdisease/alpersdisease.htm Neurodegenerative disease: Encephalopathy.] |
| *[http://www.cjd.ed.ac.uk/ UK CJD Surveillance Unit] Statistics for prion disease in the UK, information on TSEs, and a comprehensive list of other links.
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| *[http://www.cjdfoundation.org/ Creutzfeldt-Jakob Disease Foundation] Offers support and information concerning Creutzfeldt-Jakob Disease.
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| *[http://www.mad-cow-facts.com Mad Cow Disease] Info from the Center for Global Food Issues
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| *[http://thepathologicalprotein.com/ The Pathological Protein - Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases] (2003, updated online 2005). Philip Yam, [[Scientific American]] magazine writer and News Editor.
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| *[http://ec.europa.eu/research/press/1998/pr2710en.html European Symposium]
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| *[http://www.ninds.nih.gov/news_and_events/proceedings/spastic_paraplegia.htm American Symposium] | | *[http://www.ninds.nih.gov/news_and_events/proceedings/spastic_paraplegia.htm American Symposium] |
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| {{Prion diseases}} | | {{Prion diseases}} |
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| [[Category:Prions]] | | [[Category:Prions]] |
| [[Category:Transmissible spongiform encephalopathies]] | | [[Category:Transmissible spongiform encephalopathies]] |
| | [[Category:Disease]] |
| | [[Category:Neurology]] |
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| [[cs:Transmisivní spongiformní encefalopatie]] | | [[cs:Transmisivní spongiformní encefalopatie]] |
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| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |
| | <references /> |